Initially I read it as one of those “this is how near-impossible our task is!” lines, but on reflection I think it’s also probably just literally true. It’s kind of saying that making a single-player game, you have to be one of those directors who work without letting your actors know what’s going to happen, so that you can immerse them in the scene to the extent that they provide an authentic and appropriate reaction to whatever comes up.
In a game, sometimes the authentic reaction is no more complex than “Enemies?! KILL!!!!!!!” but even this is obviously a specific response that takes effort to set up. You have to have built a world and a scenario immersive enough that the player recognizes enemies, knows the game-appropriate action, and is enthusiastic about taking that action. If that’s the reaction you want from a player, then any other response is likely to be a failure of design or scene-setting.
“Enemies? Yawn,” or “Enemies? Not a-freakin’-GAIN,” are signs that the ‘lead actor’ is not engaging with the story in a way you intended, and since the lead actor is also the audience, the audience is probably not connecting with the story the way you want either.
Maybe the really challenging part is not so much that the lead actor doesn’t have a script, as that you can’t cast the lead actor. You can’t have any sense before working with the actor that he or she is the kind of person who’s likely to react to the events you’ve planned in a way that will work well with the story you’re trying to tell. You have to write and plan your script and all your shots with the knowledge that you’re going to end up casting whatever random person shows up on set.
You just hope that your ‘casting call,’ in the form of promotional materials, is going to attract the kind of actors you want, since otherwise you could wind up with a lead actor who doesn’t engage with your script in at all the way you hoped, and an audience that is bored or disappointed or filled with murderous rage.