New Spaces

I can think of three ways for a space traveler to venture into a (to him) previously unknown volume of space.

(i) Leave known space:

van Rijn may have led an expedition outside known space in his retirement;
the Aenean rebels fled around two spiral arms, through a dark nebula and into the "starfog" cluster where they colonized a planet that would never have been found if some of their descendants had not come looking for civilization.

(ii) Explore within known space:

the trader teams check systems bypassed by the interstellar frontier;
in the Imperial period, most planetary systems have had little or no contact with the Imperium so anything could be happening within Imperial borders.

(iii) Explore what is no longer "known space" during the Long Night. Roan Tom says:

"'I shook pursuit in the Nebula. But when we came out on the other side, we were in a part o' space that wasn't known to us. Old Imperial territory still, o' course, but that could mean anything.'"
-Poul Anderson, Flandry's Legacy (New York, 2012), p. 459.

Thus, the mere passage of time and history have transformed known space back into unknown space.