Measurement of Isolation in a Directional Coupler
You do not need S21 because, as you point out, you can't measure it, and you're not going to use it.

What's relevant to you is S34, the unwanted, ideally 0 reverse coupled signal.

Your directivity, the difference between the forward and the reverse coupling, is the ratio of S31 to S34.

This answer assumes you're the user of this packaged coupler. If instead you're the designer of the bare metal coupler component that's inside the package, then you will want to measure S21, but then you'll have access to all four ports of the coupler.