A wasted space is still a wasted space. Why would it matter if you had 400 billion or 4 Billion, if you are not going to visit 396 billion stars anyway. 396 Billion stars will just become background skybox nothing more.
That'd be true for a single-player game, sure. The original Elite's 2048 stars was plenty for then - I doubt very many players visited all of them (well, in the original some of them were inaccessible, but even in remakes which allowed you to get to them) though I know a few made a good attempt at doing so.
Let's say a future "Borders Development" is looking to make a vaguely Elite-like MMO in the 2040s: so, set in space, and with "exploration" as one of its primary professions. They aim to - because Borders Development is filled with only the best staff in the industry, hardware has moved on a lot, Unreal Engine 9 is looking great, and so they will obviously avoid all the previous mistakes - at least match the old Elite Dangerous' performance (not counting the Epic giveaway) and get to at least 5 million players with the game lasting over 10 years
For exploration to continue to be a primary profession for all of those 10 years, there needs to be new things to discover for most of that time. My first long-range exploration trip in Elite Dangerous wasn't a massive one by full explorer standards but took around 1000 systems, most of which were new to me.
So, let's say that the average player will take one trip of that sort of length in their career - most will do far less, some dedicated explorers will do a hundred times as much to balance out. That's 5 million times 1000 systems needed for the planned game lifetime, or 5 billion systems. Well, let's say not every one of those needs to be a first discovery, and the later players are going to get fewer of them. We can probably get by with just a billion systems.
Once you have a method which can generate a billion systems at all - or even a million systems at all [1] - you may as well go for 400 billion and make the galaxy the right shape. It doesn't get any harder to generate them after the first million [2].
But equally, you're not going to be able to hand-design even a million systems no matter how good your team is, so even by that stage you're running in to the "99.99% of them are based on fairly obvious patterns" problem. EVE - which has been going for two decades and adding them as it goes along - is I think the game with the largest number of hand-designed systems, and that's a number measured in thousands, which is nowhere near enough for exploration to be a primary profession.
"Borders Development" - because they're filled with the best staff in the industry - will conclude at this point that "exploration as a primary profession" is basically incompatible with doing any of the other professions well, and drop it before it ever gets close to being a rumour. The game will be very successful, but people will still wish it had exploration "like Elite Dangerous had back in the 2010s".
[1] Just the top ten EDSM submitters between them have a million systems. That's not sufficient for MMO-level exploration as a primary profession.
[2] The original Elite had 2048 but could have had 576,460,752,303,423,488 just as easily, even on the hardware of the time. Once you hit the "we're not doing this by hand" point, it doesn't matter how many more you do.