Heh. If you want to be cynical about it, pretty much anything anyone has a grant to research is a known unknown. We don't give money to people to look for unknown unknowns; those happen accidentally while looking for the known unknowns.

CRISPR would be an example of something that we really didn't know about popping out of research into other questions. Those kinds of discoveries are the really interesting ones, IMO: you aren't even looking for it, and suddenly, you've discovered a pathway that changes your understanding of bacterial genomics, and provides a crazy new tool for molecular biology.

I don't know if the authors of this set out to find a lymphatic duct connecting to the brain, but the existence of one was not completely unpredictable.

Sorry if I came out as cynical, that wasn't my intention. I'm genuinely interested in knowing if there any other big mysteries to solve, like this one or the neurons found in the gastrointestinal system.

You didn't. I was the one being a little cynical -- there's obviously more "known unknowns" in the world of science than those that get funding, and science does occasionally go after blue-sky research. ;-)